Friday, Dec 7, 2001
South San Francisco, Calif. -- December 7, 2001 --Genentech, Inc. today reported, in anticipation of upcoming major oncology meetings, key advancements in its portfolio of novel marketed and pipeline targeted therapies for the treatment of cancer, the number two fatal disease in the United States. Genentech's BioOncology initiative includes Rituxan® (Rituximab) and Herceptin® (Trastuzumab), the first two FDA-approved monoclonal antibodies for cancer, Avastin™ (bevacizumab) and Tarceva™ (erlotinib), currently in Phase III trials for numerous advanced cancers and a pipeline of early-stage product candidates.
"In under five years since the launch of our BioOncology initiative, we have built a premier portfolio of targeted therapies aimed at treating some of the most difficult-to-treat-cancers," said Susan D. Hellmann, M.D., MPH, Genentech's executive vice president, Development and Product Operations and chief medical officer. "We continue to see data from monoclonal antibodies such as Herceptin and Rituxan demonstrating that targeted therapies have changed the way that cancer is treated, and most importantly are part of regimens that are extending patients' lives."
Rituxan -- Two-Year Follow-up Data from Completed Phase III Study in Aggressive non-Hodgkin's Lymphoma (NHL)
Rituxan will be featured in more than 130 abstracts at this year's annual meeting of the American Society of Hematology in Orlando, FL beginning today. Featured data will include two-year follow-up of a Phase III trial conducted in Europe evaluating Rituxan with CHOP chemotherapy for aggressive NHL patients and seven year follow-up data of the first-ever Rituxan plus CHOP chemotherapy trial in indolent NHL initiated in 1994. Additional presentations will highlight investigational data on the use of Rituxan with chemotherapy as a front-line treatment for chronic lymphocytic leukemia (CLL) and single agent Rituxan use in immune thrombocytopenic purpura (ITP), a B-cell mediated autoimmune disorder.
"Rituxan has become a standard therapy for patients with NHL with more than 200,000 people treated worldwide," said Dr. Hellmann. "This year's extensive presence at ASH further demonstrates the broad areas of study for Rituxan including both malignant and non-malignant autoimmune disorders in which B-cells may play a role."
Rituxan, indicated for patients with relapsed or refractory low-grade, or follicular, CD20 positive B-cell NHL is co-marketed in the United States by Genentech and IDEC Pharmaceuticals Corporation (Nasdaq: IDPH). Roche markets Rituxan in the rest of the world, except Japan where Rituxan is co-marketed with Zenyaku Kogyo Co. Ltd.
Rituxan Safety Information
Rituxan received FDA approval in November 1997. It was approved in the European Union under the trade name MabThera® in June 1998. The majority of patients experience infusion-related symptoms with their first Rituxan infusion. These symptoms include, but are not limited to, flu-like fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema and hypotension. These symptoms vary in severity and generally are reversible with medical intervention. In rare instances, severe and fatal infusion-related reactions have occurred, nearly all of which have been associated with the first Rituxan infusion.
In rare instances, severe mucocutaneous skin reactions have occurred that may be associated with Rituxan therapy. Many of these reactions have been described as paraneoplastic pemphigus which is known to be associated with various B-cell lymphomas particularly NHL and CLL. Patients who develop a severe mucocutaneous skin reaction should have Rituxan discontinued and receive appropriate medical treatment, including a skin biopsy to guide therapy.
Avastin Completes Enrollment of Phase III Breast Cancer Study
During 2001, Genentech continued to make important progress with Avastin, the Company's leading anti-angiogenesis monoclonal antibody directed at vascular endothelial growth factor (VEGF), a common pathway of tumor growth. In December, the pivotal 400 patient Phase III clinical trial evaluating Avastin with Xeloda® (capecitabine) versus Xeloda alone for refractory metastatic breast cancer completed patient enrollment.
Avastin continues to be studied as part of a broad late stage clinical development program. In October 2001, the National Cancer Institute (NCI), Surgery Branch, announced that a Phase II study evaluating Avastin as a single agent in metastatic renal cell carcinoma (kidney cancer) had reached its pre-specified efficacy endpoint earlier than expected. Recruitment to the trial was stopped and Genentech is working closely with NCI and the FDA to determine next steps based on an independent review of the data.
In addition to these two studies, Genentech is currently enrolling previously-untreated patients into two randomized Phase III clinical trials evaluating Avastin with or without chemotherapy in metastatic colorectal cancer. The Company also is working closely with the Eastern Cooperative Oncology Group (ECOG) in conducting a Phase II/III clinical trial in previously-untreated metastatic non-small cell lung cancer patients and will initiate a Phase II/III clinical trial in previously-untreated metastatic breast cancer patients. Data suggests that Avastin was generally well-tolerated in Phase II combination trials while most adverse events seen in the studies were consistent with those of the chemotherapy regimens alone. Adverse events seen more often in the combination arms included headache, fever, chills, nosebleeds, rash hypertension, diarrhea and stomatitis, proteinura and thrombosis. Patients and clinicians interested in learning more about ongoing Avastin clinical trials should call 1-888-662-8728.
HER2 Test Receives Positive Recommendation by FDA's Oncologic Drug Advisory Committee (ODAC)
On December 5th, the FDA's ODAC panel unanimously recommended approval of a supplemental Biologics License Application (sBLA) for the inclusion of fluorescence in situ hybridization (FISH) testing, by PathVysion™ (Vysis, Inc.), as an appropriate method to determine a patient's HER2 gene amplification level.
Dr. Hellmann continued, "We are pleased with the outcome of the ODAC panel which underscores the importance of evaluating new HER2 testing methodologies with the goal of identifying only those women with HER2 positive metastatic breast cancer that are likely to benefit from Herceptin."
The recommendation for approval was based on data from an exploratory, prospectively-designed analysis demonstrating that FISH testing is reliable, accurate and has a high rate of concordance or agreement (88%) with the protein test used in Herceptin pivotal studies to identify HER2-positive breast cancer. Genentech will work closely with the FDA to determine the appropriate language for the Herceptin package insert.
Herceptin Being Studied in Early Breast Cancer
Additionally, Herceptin will be featured in numerous abstracts at the San Antonio Breast Cancer Symposium beginning on December 10th. The San Antonio meeting is one of the premier venues for physicians and investigators to present and discuss the latest developments in breast cancer treatment. At this year's meeting, pilot safety data from a cooperative group study evaluating Herceptin in early-stage (adjuvant) HER2 positive breast cancer will be presented. Additional data on Herceptin in combination with various chemotherapy agents will also be presented.
More than 10,000 women from around the world are currently being enrolled into four large randomized Phase III clinical trials evaluating the safety and efficacy of Herceptin with different chemotherapy regimens in women with HER2 positive early-stage breast cancer. Genentech is collaborating with three major cancer cooperative groups in the United States and internationally to conduct these clinical trials. A fourth trial is being conducted outside the United States by F. Hoffmann-La Roche.
Women with early-stage breast cancer or caregivers interested in learning more about the Herceptin adjuvant trials should speak with their physician and/or call the National Cancer Institute (NCI) Cancer Information Service (CIS) at 1-800-4-CANCER or visit the NCI's clinical trials website at cancertrials.nci.nih.gov.
Herceptin Safety Information
Herceptin received FDA approval in September 1998 for use as a front-line treatment in combination with paclitaxel and alone as a second- and third-line therapy for patients with HER2 positive metastatic breast cancer. Herceptin generally is well-tolerated. Overall, the most common adverse events in the pivotal trial were fever, hematologic toxicity and cardiac dysfunction. In the post-marketing setting, rare serious and fatal infusion-related events have occurred. Most patients who experienced the more serious and fatal infusion-related events had pre-existing pulmonary compromise and advanced malignancies.
The most serious adverse event in the pivotal trial was cardiac dysfunction (NYHA Grade I-IV), which occurred more frequently when Herceptin was administered with anthracycline and cyclophoshamide. A small percentage of patients had potentially severe and/or life threatening NYHA Grade III/IV toxicity. However signs and symptoms improved in 75 percent of patients, and with medical management, none of the patients receiving paclitaxel had persistent Grade III/IV cardiac dysfunction.
Leveraging HER Pathway Expertise -- Tarceva Phase III Trials Underway
For more than a decade, Genentech scientists and clinicians have been studying the biological components of the HER signaling pathway and the genesis of cancer. A majority of the scientific knowledge about the HER pathway has been elucidated by Genentech scientists and collaborators.
To further leverage the Company's understanding of the HER signaling pathway, Genentech signed a worldwide collaboration with OSI Pharmaceuticals (Nasdaq: OSIP) and Roche for Tarceva, a novel small molecule tyrosine kinase inhibitor directed against epidermal growth factor receptor (EGFR). EGFR is also known as HER1 and is involved in the growth of numerous solid tumor cancers. The collaboration has now initiated four Phase III clinical trials and numerous additional trials as part of our comprehensive worldwide clinical development program. Three of the Phase III trials are evaluating Tarceva in combination with various chemotherapy agents for non-small cell lung cancer, and the fourth trial is studying Tarceva with chemotherapy for patients with metastatic pancreatic cancer.
In 2001, Genentech also added two HER pathway-based therapies into the Company's development pipeline. During the fourth quarter of 2001, the first patient was enrolled into a Phase I study evaluating the safety of the monoclonal antibody, rhuMAb 2C4, for the treatment of non-HER2 positive cancer. RhuMAb 2C4 is designed to disrupt signaling by blocking HER2's function as a co-receptor.
Secondly, together with our partner, ImmunoGen (Nasdaq: IMGN), Genentech presented preclinical results on Trastuzumab-DM1 at the AACR/NCI/EORTC scientific meeting and moved Trastuzumab-DM1 into development. Trastuzumab-DM1 combines Herceptin with DM1, a cytotoxic agent.
"The research we have conducted in the HER pathway is an excellent example of Genentech's approach of utilizing biological expertise to identify novel cancer targets within signaling pathways involved in the genesis of cancer," said Richard Scheller, Ph.D., Genentech's senior vice president, Research. "We have built a broad integrated research approach, including our Secreted Protein Discovery Initiative (SPDI) and genomics capabilities, to identify novel targets that are involved in cancer. In addition, our efforts expand beyond the HER signaling pathway and include targets involved in angiogenesis, apoptosis and many other key cancer pathways."
Genentech, Inc. is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Fifteen of the currently approved biotechnology products stem from Genentech science. Genentech markets ten biotechnology products directly in the United States. The company has headquarters in South San Francisco, Calif. and is traded on the New York Stock Exchange under the symbol DNA.
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